3,212,970 United States Patent Office Patented Oct. 19, 1965

1. 2 mine resin complex, promethazine hydrochloride, pyr 3,212,970 athizine hydrochloride, pyrilamine maleate, pyrrobuta TREATMENT OF PSORASIS mine phosphate, thenyldiamine hydrochloride, thonzyl Joseph Glasser, 8801 Shore Road, Brooklyn, N.Y. amine hydrochloride and tripelennamine hydrochloride. No Drawing. Filed Feb. 4, 1960, Ser. No. 6,632 When employed in conjunction with a diuretic, the dosage 7 Claims. (CI. 167-65) of these antihistaminic compounds is generally that recom This invention relates to therapeutic compositions and, mended by the United States Pharmacopoeia as being the more particularly, to a therapeutic composition for al average adult dosage, although in some instances up to leviating psoriasis. The invention is based on my dis four times the normal dosage may be employed. The covery that antihistaminic compounds and diuretic com 10 minimum dosage, of course, need only be an amount suffi pounds, when used in conjunction with each other, are cient to cause a physiological reaction, which will vary capable of therapeutically alleviating psoriasis when a amongst different individuals. composition containing both compounds is internally ad The antihistaminic compound is employed in the ther ministered to a person afflicted with the disease. I have apeutic composition with a diuretic compound. My ex found in all instances that the use of either compound 15 periments indicate that any diuretic compound effectively alone has virtually no effect on the course of the disease, cooperates to some degree with an antihistaminic com the combined use of an antihistaminic compound and a pound for therapeutically alleviating psoriasis, though diuretic compound exerts a unique antipsoriatic effect some diuretic compounds, notably the organomercurial when both compounds are internally administered to diuretics as well as chlorothiazide and its derivatives, are gether to a psoriatic. 20 more effective than others. Satisfactory diuretic com Psoriasis is a chronic inflammatory skin disease char pounds for use in the antipsoriatic composition of the acterized by the development of reddish patches covered invention include such commercially available diuretic with silvery-white imbricated scales. The disease espe compounds as acetazoleamide, aminometradine, amino cially affects the extensor surfaces of the body and the phylline, amisometradine, ammonium chloride, carbacryl scalp. However, the etiology and pathogenesis of psori 25 amine resin, carboxylic resins, chlormerodrin, chloro asis have remained somewhat obscure, and consequently thiazide, choline theophyllinate, hydrochlorothiazide, no rational basis for the treatment of the disease has been magnesium theophyllinate, meralluride, mercaptomerin, evolved. mercurmatilin, mercurital, mercurophylline, merethoxyl By administering standard dosages of an antihistaminic line procaine, mersalyl and theophylline, styronate resins, and a diuretic at the same time, I have found that both 30 theobromine, theophylline, theophylline isopropanola compounds are capable of exerting a unique antipsoriatic mine, theophylline methylglucamine, theophylline mono effect when used in combination, although the use of ethanolamine, theophylline sodium glycinate, and urea. either compound by itself has no apparent effect on the As in the case of the antihistaminics, the minimum dosage course of the disease. When a composition containing of these diuretic compounds is that amount sufficient to both an antihistaminic compound and a diuretic com 35 cause a physiological reaction, although the normal pound is administered to a psoriatic patient either by in dosage will be that recommended for the particular di jection (intramuscularly) or orally, the psoriatic lesions uretic compound in the United States Pharmacopoeia. either disappear completely or undergo a marked diminu Both the antihistaminic compound and the diuretic tion in size and intensity. compound may be prepared in the form of an injectable Accordingly, the therapeutic composition of the inven 40 solution, using water or some other pharmacologically tion comprises an antihistaminic compound and a diuretic acceptable solvent, or they may be compounded into a compound, each in amounts sufficient to cause a phys tablet for oral ingestion, depending upon the mode of iological reaction. This composition may be prepared in therapy selected by the physician. The frequency of the form of an injectable solution for administration in therapy, of course, will depend upon the individual tramuscularly, or it may be compounded into a tablet for 45 tolerances of the psoriatic patient undergoing treatment, oral administration, the dosage in each case depending but as a general rule, the response of each patient will upon the particular antihistaminic and diuretic employed. be directly proportional to the number of times the com Any antihistaminic compound or any compound which position is administered rather than the time interval in functions pharmacologically as a histamine antagonist which treatment is given. may be used in conjunction with a diuretic to prepare the 50 Upon administration of the therapeutic composition of antipsoriatic composition of the invention, selection of a the invention to a psoriatic patient, there generally is a suitable antihistaminic compound being limited solely by disappearance or marked diminution of itching within a availability. Particularly satisfactory results may be ob 48-hour period. Continued treatment generally results tained by using such commercially available antihistiminic in diminished scaling within the week, and the lesions compounds as antazoline hydrochloride, bromodiphenhy 55 gradually begin to lose their inflamed character, to be dramine hydrochloride, buclizine hydrochloride, chlor come salmon-pink in color, and to lose their character cyclizine hydrochloride, chlorothen citrate, chlorphenira istic induration. Prolonged treatment, generally lasting mine maleate, cyclizine hydrochloride, cyclizine lactate, for five weeks or more, results in the appearance of islets dimenhydrinate, diphenhydramine hydrochloride, di of normal skin in the central or peripheral portions of phenylpyraline hydrochloride, dosoxylamine Succinate, 60 the psoriaformed area. These islets of normal skin doxylamine succinate, isothipendyl hydrochloride, me gradually merge together as the lesions become lighter clizine hydrochloride, methafurylene fumarate, methal in color and eventually disappear altogether. latal, methaphenilene hydrochloride, methapyrilene hy Table I sets forth the results of as eries of clinical drochloride, methylaminophenylthenylpiperidine tartrate, tests in which a number of psoriatic patients were paren parabromidylamine maleate, paracarbinoxamine maleate, 65 terally treated with the antipsoriatic composition of the phenindamine tartrate, pheniramine maleate, phenyl invention. The severity of the disease in each of these toloxamine dihydrogen citrate and sulfate, phenyltoloxa patients varied from a minimal localized eruption (Class 3,212,970 3 4. I), to small scattered eruptions (Class II), to moderately chloride, and said diuretic compound being selected from evere eruptions in which the lesions were discreet but the group consisting of acetazoleamide, aminometradine, generalized (Class III), and finally to diffuse generalized aminophylline, amisometradine, ammonium chloride, eruptions (Class IV). Each patient received an intra carbacrylamine resin, carboxylic resins, chlormerodrin, muscular injection at least once every other day. The chlorothiazide, choline theophyllinate, hydrochlorothi dosage for the first five injections contained 20 mg. of azide, magnesium theophyllinate, meralluride, mercap chlorpheniramine maleate, 100 mg. of mersalyl, and 50 tomerin mercurmatilin, mercurital, mercurophylline, mg. of theophyllin, which was doubled after the fifth in merethoxyline procaine, mersalyl and theophylline, jection. The percentage improvement in each case, styronate resins, theobromine, theophylline, theophylline which was measured by a complete disappearance (corre isopropanolamine, theophylline methylglucamine, theo sponding to 100 percent) or a corresponding diminution phylline monoethanolamine, theophylline sodium glycin in the intensity of the lesions is tabulated in Table I. ate, and urea. TABLE I Treatment of psoriasis

Duration of Number Number Percent No. Case Sex Age Disease Severity of Weeks of Injec Improve Prior to of Treat tions ment Treatment (years) ment

H.B. F 37 14 II. 70 100 A.B- M 48 23 IV 25 60 M.C. F 48 12 IV 38 70 A.L. M 30 14 III 21 A.F.--- F. 40 30 III 60 R. 55 45 V 63 50 A. 37 34 IV 27 100 C. 39 28 IV 79 1OO R. 35 3 I 17 100 H. 39 26 V 92 90 L. 59 18 II 40 00 F. 54 34 IW 29 90 A. 48 12 V 64 90 D. 31 2 II 23 90 K. 29 0 III 24 70 N. 60 3 I 28 40 S. 28 16 IV 60 70 B. 51 40 IV 19 100 B. 44 36 V 38 60 C. 56 25 II 2. 30 M. 23 (1) II. 28 50 ID. 55 7 III 6 100 A. 37 3 III 2 200 J.B------32 25 V 52 90

16 months. Although each of the foregoing clinical tests have dem 3. The method of alleviating psoriasis according to onstrated the results obtained when a psoriatic patient claim 2, in which the diuretic compound is chlorothiazide. undergoes parenteral treatment using the antipsoriatic 4. The method of alleviating psoriasis according to composition, comparable results may be attained by ad claim 2, in which the diuretic compound is hydrochloro ministering the composition orally. thiazide. I claim: 45 5. The method of alleviating psoriasis which comprises 1. The method of alleviating psoriasis wihch com administering to a psoriatic patient an intramuscular in prises internally administering to a psoriatic patient a jection of a therapeutic composition comprising about 20 therapeutic composition comprising an antihistaminic mg of chlorpheniramine maleate, and about 150 mg. of compound and a diuretic compound in an amount suffi meralluride until the psoriatic lesions diminish. cient to cause a physiological reaction until the psoriatic 50 6. The method of alleviating psoriasis which comprises lesions diminish. internally administering to a psoriatic patient a therapeu 2. The method of alleviating psoriasis which com tic composition comprising about 20 mg. of chlorphenir prises internally administering to a psoriatic patient a amine maleate, and about 150 mg. of meralluride until therapeutic composition comprising an antihistaminic the psoriatic lesions diminish. compound and a diuretic compound in an amount suffi 7. The method of alleviating psoriasis which comprises cient to cause a physiological reaction until the psoriatic internally administering to a psoriatic patient a thera lesions diminish, said antihistaminic compound beng Se peutic composition comprising an antihistaminic com lected from the group consisting of antazoline hydrochlo pound and meralluride in amounts sufficient to cause a ride, bromodiphenhydramine hydrochloride, buclizine hy 60 physiological reaction until the psoriatic lesions diminish, drochloride, chlorcyclizine, hydrochloride, chlorothen said antihistaminic compound being selected from the citrate, chlorpheniramine maleate, cyclizine hydrochlo group consisting of antazoline hydrochloride, bromodi ride, cyclizine lactate, dimenhydrinate, diphenhydramine phenhydramine hydrochloride, buclizine hydrochloride, hydrochloride, diphenylpyraline hydrochloride, dosoxyl chlorcyclizine hydrochloride, chlorothen citrate, chlor amine succinate, doxylamine succinate, isothipendyl hy 65 pheniramine maleate, cyclizine hydrochloride, cyclizine drochloride, meclizine hydrochloride, methafurylene lactate, dimenhydrinate, diphenhydramine hydrochloride, fumarate, methallatal, methapheniline hydrochloride, diphenylpyraline hydrochloride, dosoxylamine succinate, methapyrilene hydrochloride, methylaminophenylthenyl doxylamine Succinate, isothipendyl hydrochloride, mecli piperidine tartrate, parabromidylamine maleate, paracar Zine hydrochloride, methafurylene fumarate, methallatal, binoxamine maleate, phenindamine tartrate, pheniramine 70 methaphenilene hydrochloride, methapyrilene hydrochlo maleate, phenyltoloxamine dihydrogen citrate and sulfate, ride, methylaminophenylthenylpiperidine tartrate, para phenyltoloxamine resin complex, promethazine hydro brondylamine maleate, paracarbinoxamine maleate, chloride, pyrathizine hydrochloride, pyrilamine maleate, phenindamine tartrate, pheniramine maleate, phenyltolox pyrrobutamine phosphate, thenyldiamine hydrochloride, amine dihydrogen citrate and sulfate, phenyltoloxamine thonzylamine hydrochloride, and tripelannamine hydro resin complex, promethazine hydrochloride, pyrathizine 3,212,970 5 6 hydrochloride, pyrilamine maleate, pyrrobutamine phos OTHER REFERENCES phate, thenyldiamine hydrochloride, thonzylamine hydro Bolgert: Metal, "Cure of a Case of Generalized Psori chloride, and tripelannamine hydrochloride. asis by Intramuscular Injections of Distilled Water,” Bull. Soc. fr. der syph (Paris), 62 (1), pp. 50-51, January References Cited by the Examiner February 1955. UNITED STATES PATENTS Bristol Laboratories, Great Britain 759,577, Oct. 2,070,080 2/37 Hart ------167 71 17, 1956. 2,754,296 7/56 Stuttgen ------260-211 Downing, J. G.: "Medical Progress-Dermatology 2,766,174 10/56 Foley et al. ------167-65 Psoriasis,' New England J. of Medicine, 260 (24, pp. 2,766,175 10/56 Klemme ------167-71. O 1223-1228, June 11, 1959. 2,768,115 10/56 Buckwalter et al. ------167-82 “N.N.D., 1960, New and Non-Official Drugs, A.M.A. 2,776,970 1/57 Lintner ------230-239.65 Council on Drugs, Library of Congress No. 9, 1271 2,791,609 5/57 Kaplan ------260-559 (Jan. 29, 1960), J. B. Lippincott Co., Philadelphia, Pa., 2,795,528 6/57 Buckwalter et al. ------67-55 entry “Antihistamines,” pp. 17-36; entry "Xanthine De 2,813,861 11/57 Schlesinger et al. ------260-242 rivatives, pp. 420-425; "Renal-Acting and Edema-Re 2,824,869 2/58 Buckwalter et al. ------260-210 ducing Agents,' pp. 654-675. 2,854,378 9/58 BuckWalter ------167-64 2,887,481 5/59 Sherlock et al. ------260-243 “Tedral Anti-H. Tablets' (W.C.), T.M. 683,159, reg 2,928,833 3/60 Leake et al. ------260-253 istered Aug. 11, 1949 (date of first use in commerce 2,931,798 4/60 Umezawa et al. ------260-210 20 May 26, 1958). 2,949,470 8/60 Schlesinger et al. ----- 260-326.3 2,951,014 8/60 Garman ------167-82 LEWIS GOTTS, Primary Examiner. 2,996,431 8/61 Barry ------167-82 SAM ROSEN, MORRIS O. WOLK, Examiners.